Hermansky S J, Mohammadpour H A, Murray W J, Stohs S J
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha.
Pharmacology. 1987;35(6):301-7. doi: 10.1159/000138354.
Thyroid hormones have been implicated in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Therefore, the effects of methimazole (MMI) and propylthiouracil (PTU) induced hypothyroidism and surgical thyroidectomy on several toxic manifestations of TCDD were investigated. Female rats were treated with MMI (0.50 mg/kg) for 10 or 28 days, or PTU (5.0 mg/kg) for 10 days. Other animals were surgically thyroidectomized. The animals received TCDD (100 micrograms/kg) orally or the corn oil vehicle 6 days prior to sacrifice. MMI and PTU decreased serum thyroxine (T4) levels by 27-33% while surgical thyroidectomy decreased T4 levels by 66%. TCDD alone decreased T4 levels by 67%, and similar effects occurred in MMI and PTU treated animals. TCDD produced a 9% increase in serum triiodothyronine (T3) concentrations, and neither MMI or PTU treatment for 10 days modified this effect. Neither antithyroid drug prevented TCDD induced weight loss. TCDD administration resulted in over a 300% increase in hepatic malondialdehyde (MDA) content and a 60% decrease in glutathione peroxidase activity. Neither antithyroid compound affected TCDD-induced alterations in these two parameters. TCDD enhanced MDA content by 220% and inhibited glutathione peroxidase activity by 39% in surgically thyroidectomized rats. Thus, only severe hypothyroidism produced by surgical thyroidectomy was able to partially prevent the effects of TCDD on hepatic MDA content and glutathione peroxidase activity.
甲状腺激素与2,3,7,8-四氯二苯并对二恶英（TCDD）的毒性有关。因此，研究了甲巯咪唑（MMI）和丙硫氧嘧啶（PTU）诱导的甲状腺功能减退以及手术甲状腺切除术对TCDD几种毒性表现的影响。给雌性大鼠用MMI（0.50mg/kg）处理10天或28天，或用PTU（5.0mg/kg）处理10天。其他动物进行手术甲状腺切除。在处死前6天，给动物口服TCDD（100微克/千克）或玉米油载体。MMI和PTU使血清甲状腺素（T4）水平降低27 - 33%，而手术甲状腺切除术使T4水平降低66%。单独TCDD使T4水平降低67%，在MMI和PTU处理的动物中也出现类似效果。TCDD使血清三碘甲状腺原氨酸（T3）浓度增加9%，MMI或PTU处理10天均未改变这种作用。两种抗甲状腺药物均不能预防TCDD诱导的体重减轻。给予TCDD导致肝脏丙二醛（MDA）含量增加超过300%，谷胱甘肽过氧化物酶活性降低60%。两种抗甲状腺化合物均未影响TCDD诱导的这两个参数的改变。在手术甲状腺切除的大鼠中，TCDD使MDA含量增加220%，并使谷胱甘肽过氧化物酶活性抑制39%。因此，只有手术甲状腺切除术导致的严重甲状腺功能减退能够部分预防TCDD对肝脏MDA含量和谷胱甘肽过氧化物酶活性的影响。
